Abstract
Mild traumatic brain injury (mTBI, cerebral concussion) is a risk factor for the development of psychiatric illness such as posttraumatic stress disorder (PTSD). We sought to evaluate how omega-3 fatty acids during brain maturation can influence challenges incurred during adulthood (transitioning to unhealthy diet and mTBI) and predispose the brain to a PTSD-like pathobiology. Rats exposed to diets enriched or deficient in omega-3 fatty acids (n-3) during their brain maturation period, were transitioned to a western diet (WD) when becoming adult and then subjected to mTBI. TBI resulted in an increase in anxiety-like behavior and its molecular counterpart NPY1R, a hallmark of PTSD, but these effects were more pronounced in the animals exposed to n-3 deficient diet and switched to WD. The n-3 deficiency followed by WD disrupted BDNF signaling and the activation of elements of BDNF signaling pathway (TrkB, CaMKII, Akt and CREB) in frontal cortex. TBI worsened these effects and more prominently in combination with the n-3 deficiency condition. Moreover, the n-3 deficiency primed the immune system to the challenges imposed by the WD and brain trauma as evidenced by results showing that the WD or mTBI affected brain IL1β levels and peripheral Th17 and Treg subsets only in animals previously conditioned to the n-3 deficient diet. These results provide novel evidence for the capacity of maladaptive dietary habits to lower the threshold for neurological disorders in response to challenges.
Highlights
The balance between brain health and disease is often unpredictable and likely dependent on poorly understood vulnerability factors acquired during early life [1,2]
Anxiety-like behavior after Adult Brain Trauma We assessed the impact of dietary transition as determinant factor for the outcome of mild traumatic brain injury on anxiety-like behavior
Dietary n-3 deficiency resulted in anxiety-like behavior as reflected by a significant reduction in time spent in open arms of elevated plus maze (EPM), which was further aggravated after transition to the western diet (WD) (Figure 2A)
Summary
The balance between brain health and disease is often unpredictable and likely dependent on poorly understood vulnerability factors acquired during early life [1,2]. We have embarked in studies to understand how dietary omega-3 fatty acid during brain maturation influences the capacity of the brain to cope with later challenges. Post-traumatic stress disorder (PTSD) has emerged as a mysterious condition in which individuals exposed to trauma develop high levels of anxiety and inability to cope with routine living conditions [5]. Among of the few clues, we know that a large number of victims exposed to episodes of brain trauma develop PTSD, likely influenced by some pre-existing conditions. We present evidence that switching from omega-3 fatty acids deficiency during brain formation to a diet high in calories in adult life weaken the substrates for brain plasticity and predispose the brain to elevated anxiety-like behavior
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